Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this trial is to determine the efficacy and safety of an investigational drug in patients with type 2 diabetes mellitus.
Interventions
DRUGsitagliptin phosphate
sitagliptin phosphate 25 mg, 50 mg, 100 mg QD, or 200 mg QD 12-weeks.
DRUGComparator: placebo (unspecified)
placebo QD 12-weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with type 2 diabetes mellitus
Exclusion criteria
* Patients with type 1 diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at Week 12 | Baseline and Week 12 | HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the Week 0 HbA1c percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Albumin at Week 12 | Baseline and Week 12 | Change from baseline at Week 12 is defined as Week 12 minus Week 0. |
| Change From Baseline in Fasting Plasma Glucose at Week 12 | Baseline and Week 12 | Change from baseline at Week 12 is defined as Week 12 minus Week 0. |
Participant flow
Recruitment details
Phase II. First patient in: 11 July 2005. Last patient, last visit: 8 March 2006. The study was conducted at 97 centers in Japan.
Pre-assignment details
Patients 20-75 years of age with type 2 diabetes mellitus and inadequate glycemic control (HbA1c ≥6.5% and \<10% at Week -2) were eligible for randomization following at least 8 weeks of diet/exercise and antihyperglycemic agent (AHA) wash-off (for patients previously on an AHA), including a 2-week placebo run-in.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 25 mg QD The Sitagliptin 25 mg group includes data from all patients randomized to receive treatment with sitagliptin 25 mg orally once daily (QD=once daily). | 80 |
| Sitagliptin 50 mg QD The Sitagliptin 50 mg group includes data from all patients randomized to receive treatment with sitagliptin 50 mg orally once daily (QD=once daily). | 72 |
| Sitagliptin 100 mg QD The Sitagliptin 100 mg group includes data from all patients randomized to receive treatment with sitagliptin 100 mg orally once daily (QD=once daily). | 70 |
| Sitagliptin 200 mg QD The Sitagliptin 200 mg group includes data from all patients randomized to receive treatment with sitagliptin 200 mg orally once daily (QD=once daily). | 68 |
| Placebo The Placebo group includes data from all patients randomized to receive treatment with matching placebo orally once daily. | 73 |
| Total | 363 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 1 | 0 |
| Overall Study | Adverse event in pre-treatment period | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 2 | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Sitagliptin 25 mg QD | Sitagliptin 50 mg QD | Sitagliptin 100 mg QD | Sitagliptin 200 mg QD | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 59.9 years STANDARD_DEVIATION 7.9 | 60.2 years STANDARD_DEVIATION 9.4 | 58.3 years STANDARD_DEVIATION 9.5 | 60.6 years STANDARD_DEVIATION 7.7 | 60.2 years STANDARD_DEVIATION 8 | 59.8 years STANDARD_DEVIATION 8.5 |
| Fasting Plasma Glucose (FPG) | 145.7 mg/dL STANDARD_DEVIATION 37.6 | 144.3 mg/dL STANDARD_DEVIATION 29 | 142.6 mg/dL STANDARD_DEVIATION 31.8 | 148.4 mg/dL STANDARD_DEVIATION 33.3 | 156.5 mg/dL STANDARD_DEVIATION 35.1 | 147.5 mg/dL STANDARD_DEVIATION 33.8 |
| Glycosylated albumin | 21.5 percent STANDARD_DEVIATION 3.9 | 22.0 percent STANDARD_DEVIATION 4.2 | 21.9 percent STANDARD_DEVIATION 4.5 | 21.9 percent STANDARD_DEVIATION 3.9 | 23.7 percent STANDARD_DEVIATION 4.5 | 22.2 percent STANDARD_DEVIATION 4.3 |
| Hemoglobin A1c (HbA1c) | 7.5 percent STANDARD_DEVIATION 0.8 | 7.6 percent STANDARD_DEVIATION 0.8 | 7.6 percent STANDARD_DEVIATION 0.8 | 7.7 percent STANDARD_DEVIATION 0.8 | 7.7 percent STANDARD_DEVIATION 0.9 | 7.6 percent STANDARD_DEVIATION 0.8 |
| Sex: Female, Male Female | 29 Participants | 25 Participants | 34 Participants | 28 Participants | 23 Participants | 139 Participants |
| Sex: Female, Male Male | 51 Participants | 47 Participants | 36 Participants | 40 Participants | 50 Participants | 224 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / — | 25 / — | 32 / — | 20 / — | 29 / — |
| serious Total, serious adverse events | 0 / — | 1 / — | 0 / — | 2 / — | 0 / — |
Outcome results
Primary
Change From Baseline in HbA1c at Week 12
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the Week 0 HbA1c percent.
Time frame: Baseline and Week 12
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. For FAS patients with no data at Week 12, the last non-baseline observed measurement was carried forward to Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 25 mg QD | Change From Baseline in HbA1c at Week 12 | -0.41 Percent |
| Sitagliptin 50 mg QD | Change From Baseline in HbA1c at Week 12 | -0.71 Percent |
| Sitagliptin 100 mg QD | Change From Baseline in HbA1c at Week 12 | -0.69 Percent |
| Sitagliptin 200 mg QD | Change From Baseline in HbA1c at Week 12 | -0.76 Percent |
| Placebo | Change From Baseline in HbA1c at Week 12 | 0.28 Percent |
p-value: <0.001Tukeys linear trend test based on ANCOVA
p-value: <0.00195% CI: [-1.21, -0.86]Pairwise comparison based on ANCOVA
p-value: <0.00195% CI: [-1.14, -0.79]Pairwise comparison based on ANCOVA
p-value: <0.00195% CI: [-1.16, -0.82]Pairwise comparison based on ANCOVA
p-value: <0.00195% CI: [-0.85, -0.52]Pairwise comparison based on ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 12
Change from baseline at Week 12 is defined as Week 12 minus Week 0.
Time frame: Baseline and Week 12
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. For FAS patients with no data at Week 12, the last non-baseline observed measurement was carried forward to Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose at Week 12 | -9.6 mg/dL |
| Sitagliptin 50 mg QD | Change From Baseline in Fasting Plasma Glucose at Week 12 | -11.4 mg/dL |
| Sitagliptin 100 mg QD | Change From Baseline in Fasting Plasma Glucose at Week 12 | -14.6 mg/dL |
| Sitagliptin 200 mg QD | Change From Baseline in Fasting Plasma Glucose at Week 12 | -16.9 mg/dL |
| Placebo | Change From Baseline in Fasting Plasma Glucose at Week 12 | 6.3 mg/dL |
p-value: <0.00195% CI: [-29.8, -16.6]Pairwise comparison based on ANCOVA
p-value: <0.00195% CI: [-27.4, -14.3]Pairwise comparison based on ANCOVA
p-value: <0.00195% CI: [-24.2, -11.2]Pairwise comparison based on ANCOVA
p-value: <0.00195% CI: [-22.3, -9.6]Pairwise comparison based on ANCOVA
Secondary
Change From Baseline in Glycosylated Albumin at Week 12
Change from baseline at Week 12 is defined as Week 12 minus Week 0.
Time frame: Baseline and Week 12
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. For FAS patients with no data at Week 12, the last non-baseline observed measurement was carried forward to Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 25 mg QD | Change From Baseline in Glycosylated Albumin at Week 12 | -1.9 Percent |
| Sitagliptin 50 mg QD | Change From Baseline in Glycosylated Albumin at Week 12 | -2.6 Percent |
| Sitagliptin 100 mg QD | Change From Baseline in Glycosylated Albumin at Week 12 | -2.6 Percent |
| Sitagliptin 200 mg QD | Change From Baseline in Glycosylated Albumin at Week 12 | -2.9 Percent |
| Placebo | Change From Baseline in Glycosylated Albumin at Week 12 | 0.7 Percent |
p-value: <0.00195% CI: [-4.3, -3]Pairwise comparison based on ANCOVA
p-value: <0.00195% CI: [-3.9, -2.6]Pairwise comparison based on ANCOVA
p-value: <0.00195% CI: [-3.9, -2.7]Pairwise comparison based on ANCOVA
p-value: <0.00195% CI: [-3.2, -2]Pairwise comparison based on ANCOVA